Ken Miyazawa

Accurate pre-surgical determination for self-drilling miniscrew implant placement using surgical guides and cone-beam computed tomography

Miniscrew implants have proven to be effective in providing absolute orthodontic anchorage. However, as self-drilling miniscrew implants have become more popular, a problem has emerged, i.e. root contact, which can lead to perforation and other root injuries. To avoid possible root damage, a surgical guide was fabricated and cone-beam computed tomography (CBCT) was used to incorporate guide tubes drilled in accordance with the planned direction of the implants. Eighteen patients (5 males and 13 females; mean age 23.8 years; minimum 10.7, maximum 45.5) were included in the study. Forty-four self-drilling miniscrew implants (diameter 1.6, and length 8 mm) were placed in interradicular bone using a surgical guide procedure, the majority in the maxillary molar area. To determine the success rates, statistical analysis was undertaken using Fishers exact probability test. CBCT images of post-surgical self-drilling miniscrew implant placement showed no root contact (0/44). However, based on CBCT evaluation, it was necessary to change the location or angle of 52.3 per cent (23/44) of the guide tubes prior to surgery in order to obtain optimal placement. If orthodontic force could be applied to the screw until completion of orthodontic treatment, screw anchorage was recorded as successful. The total success rate of all miniscrews was 90.9 per cent (40/44). Orthodontic self-drilling miniscrew implants must be inserted carefully, particularly in the case of blind placement, since even guide tubes made on casts frequently require repositioning to avoid the roots of the teeth. The use of surgical guides, fabricated using CBCT images, appears to be a promising technique for placement of orthodontic self-drilling miniscrew implants adjacent to the dental roots and maxillary sinuses.

Experimental tooth movement-induced osteoclast activation is regulated by sympathetic signaling.

Experimental tooth movement (ETM) changes the distribution of sensory nerve fibers in periodontal ligament and the bone architecture through the stimulation of bone remodeling. As the sympathetic nervous system is involved in bone remodeling, we examined whether ETM is controlled by sympathetic signaling or not. In male mice, elastic rubber was inserted between upper left first molar (M1) and second molar (M2) for 3 or 5 days. Nerve fibers immunoreactive for not only sensory neuromarkers, such as calcitonin gene-related peptide (CGRP), but also sympathetic neuromarkers, such as tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were increased in the periodontal ligament during ETM. To elucidate the effect of the sympathetic signal mediated by ETM, mice were intraperitoneally injected with a β-antagonist, propranolol (PRO: 20 μg/g/day), or a β-agonist, isoproterenol (ISO: 5 μg/g/day) from 7 days before ETM. PRO treatment suppressed the amount of tooth movement by 12.9% in 3-day ETM and by 32.2% in 5-day ETM compared with vehicle treatment. On the other hand, ISO treatment increased it. Furthermore, ETM remarkably increased the osteoclast number on the bone surface (alveolar socket) (Oc.N/BS) in all drug treatments. PRO treatment suppressed Oc.N/BS by 39.4% in 3-day ETM, while ISO treatment increased it by 32.1% in 3-day ETM compared with vehicle treatment. Chemical sympathectomy using 6-hydroxydopamine (6-OHDA: 250 μg/g) showed results similar to those for PRO treatment in terms of both the amount of tooth movement and osteoclast parameters. Our data showed that blockade of sympathetic signaling inhibited the tooth movement and osteoclast increase induced by ETM, and stimulation of sympathetic signaling accelerated these responses. These data suggest that the mechano-adaptive response induced by ETM is controlled by sympathetic signaling through osteoclast activation.

IGF2 modulates the microenvironment for osteoclastogenesis.

We previously reported that hypoxic stress enhanced osteoclast differentiation via increasing insulin-like growth factor 2 (IGF2) production. However, the mechanisms underlying IGF2 stimulation remains unknown. In this study, we investigated the molecular mechanisms of osteoclastogenesis by IGF2 treatment. Primary mouse bone marrow cells were cultured with IGF2. Total RNAs were applied to a DNA microarray analysis, and quantitative RT-PCR was then used to confirm the microarray data and clarify which cells expressed the relative genes. The most interesting findings were the upregulations of CXC chemokine ligand 7 (CXCL7) expression in stromal cells and stromal cell-derived factor 1 (SDF1) expression in osteoblastic cells with IGF2 treatment. The addition of exogenous SDF1 to CXCL7 increased the number of osteoclasts and promoted the formation of giant osteoclasts. These results suggest that IGF2 modulates the microenvironment around osteoclast precursor cells. SDF1 together with CXCL7 may promote the formation of giant osteoclasts.

Enhancement of Crude Bone Morphogenetic Protein-Induced New Bone Formation and Normalization of Endochondral Ossification by Bisphosphonate Treatment in Osteoprotegerin-Deficient Mice

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. We investigated both the quantity and quality of heterotopic new bone induced by crude bone morphogenetic protein (BMP) as a means of examining bone metabolism by bisphosphonate administration in OPG−/− mice. Four weeks after implantation of crude BMP, the volume of heterotopic new bone in OPG−/− mice without alendronate was significantly less than in wild-type (WT) mice. Alendronate treatment of OPG−/− mice resulted in enhancement of the volume of heterotopic new bone. Histological findings revealed that WT mice showed normal bone formation with persistent cartilage that was interspersed with islands of bone. In contrast, the cartilage was replaced by trabecular bone and bone marrow adipocytes in OPG−/− mice without alendronate. However, some cartilage was still present in OPG−/− mice with alendronate compared to those without alendronate. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG−/− mice with alendronate than in those without alendronate. These findings suggest that in stimulated osteoclastogenesis without OPG, osteoinductive activity induced by crude BMP is inhibited and endochondral ossification induced by crude BMP is accelerated. On the other hand, alendronate treatment of OPG−/− mice caused osteoinductive activity induced by crude BMP to increase and endochondral ossification induced by crude BMP to be decelerated. In conclusion, inhibition of stimulated osteoclastogenesis results in the enhancement of new bone formation and normalization of endochondral ossification.

Effectiveness of en-masse retraction using midpalatal miniscrews and a modified transpalatal arch: Treatment duration and dentoskeletal changes

Objective The purpose of this study was to compare the treatment duration and dentoskeletal changes between two different anchorage systems used to treat maxillary dentoalveolar protrusion and to examine the effectiveness of en-masse retraction using two miniscrews placed in the midpalatal suture. Methods Fifty-seven patients (9 men, 48 women), who had undergone level anchorage system treatment at Aichi-Gakuin University Dental Hospital (Nagoya, Japan) were divided into two groups according to the method of maxillary posterior anchorage reinforcement: midpalatal miniscrews (25 patients, mean age 22 years) and conventional anchorage (32 patients, mean age 19 years). The en-masse retraction period, overall treatment duration, pre-treatment effective ANB angle, and change in the effective ANB angle were compared with an independent-samples t-test. Results Compared to the headgear group, the duration of en-masse retraction was longer by approximately 4 months in the miniscrew group (p < 0.001). However, we found no significant difference in the total treatment duration between the groups. Moreover, a greater change in the effective ANB angle was observed in patients treated with miniscrews than in those treated with the conventional method (p < 0.05). Conclusions The level anchorage system treatment using miniscrews placed in the midpalatal area will allow orthodontists more time to control the anterior teeth during en-masse retraction, without increasing the total treatment duration. Furthermore, it achieves better dentoskeletal control than does the conventional anchorage method, thereby improving the quality of the treatment results.

Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement

Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.

Effect of Reveromycin A on Experimental Tooth Movement in OPG−/− Mice

In osteoprotegerin-deficient (OPG−/−) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG−/− mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG−/− and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG−/− mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG−/− mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG−/− mice.

Stabilization of tooth movement by administration of reveromycin A to osteoprotegerin-deficient knockout mice.

INTRODUCTION In this study, mechanical stress in the form of tooth movement was applied to osteoprotegerin-deficient knockout mice, which served as an animal model for juvenile Pagets disease. To compare and evaluate bone turnover and response of the surrounding bony tissue, we administered reveromycin A. We also investigated the ability of reveromycin A to control osteoclastic activity in juvenile Pagets disease. METHODS Eight-week-old male osteoprotegerin-deficient knockout and wild-type mice were injected with reveromycin A (15 mg/kg of body weight) intraperitoneally twice daily. An elastic module was inserted interproximally between the maxillary left first and second molars. RESULTS Administration of reveromycin A to osteoprotegerin-deficient knockout mice reduced tooth movement distances, increased bone volumes at the interradicular septum, decreased osteoclast counts, and reduced serum alkaline phosphatase and tartrate resistant acid phosphatase. Reveromycin A administration also caused a temporal shift in peak Runx2 staining in osteoprotegerin-deficient knockout mice so that the overall staining time course was similar to that observed for wild-type mice. CONCLUSIONS Reveromycin A administration in osteoprotegerin-deficient knockout mice inhibited bone resorption and normalized bone formation. As a result, normal bone turnover was obtained.

Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. In this study, we used human bone marrow cells (BMCs) to investigate the role of hypoxic exposure on human osteoclast (OC) formation in the presence of tumor necrosis factor (TNF). Exposing the BMCs to 3%, 5%, or 10% O2 in the presence of receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, consistent with OCs. The addition of TNF under hypoxic conditions generated significantly greater numbers of mature OCs with more nuclei than OCs generated under normoxic conditions. Longer initial hypoxic exposure increased the number of OC precursor cells and facilitated the differentiation of OC precursor cells into multinucleated OCs. Quantitative RT-PCR analysis revealed that RANKL and TNFR1 were expressed at higher levels in non-OC cells from BMCs under hypoxic conditions than under normoxic conditions. Furthermore, to confirm the involvement of TNF-induced signaling, we examined the effects of blocking antibodies against TNFR1 and TNFR2 on OC formation under hypoxic conditions. The TNFR1 antibody was observed to significantly suppress OC formation. These results suggest that hypoxic exposure plays an important role in TNF-induced osteoclastogenesis from human BMCs.

Bone morphogenetic protein-induced heterotopic bone in osteopetrosis.

The objectives of the present research on the osteopetrotic mouse are to investigate the factors influencing heterotopic bone development. The osteopetrotic mutant was deficient in macrophage colony stimulating factor and failed to activate functioning monocytes, macrophages, and osteoclasts. Macrophage colony stimulating factor deficiency also caused a heretofore undescribed delay in organization and absorption of hematomas resulting from surgical operations. Surgically implanted in a heterotopic site, bone morphogenetic protein induced approximately 10% more bone in osteopetrotic than littermate +/? mice. Radiographically, the heterotopic bone was at least 50% denser than new bone. The new bone was metachromatic or slightly basophilic rather than eosinophilic and undermined with large deposits of hypercalcified hypertrophic cartilage. Bone mineral in the osteopetrotic mouse was deposited in an apatite-like form with a higher calcium/phosphorus ratio than the bone of +/? littermates. High levels of alkaline phosphatase synthesis were sustained longer in the osteopetrotic mouse than in the +/? littermate. Tartrate resistant acid phosphatase synthesis was almost nil in osteopetrotic mice during the first 4 weeks, and thereafter appeared coincidental with spontaneous remission of osteopetrosis at 6 weeks. Implants of the mineralized cortical bone matrix of the osteopetrotic mouse showed minimal if any bone morphogenetic protein activity of matrix of +/? littermate or otherwise normal mice. The cause of the remission of the bone disorder in the osteopetrotic mouse is not known but is of great interest to students studying the problem of coupling of bone formation to bone resorption.